用于修复感染性颅骨缺损的抗菌、导电和骨相容性聚磷腈微支架。

Antibacterial, conductive, and osteocompatible polyorganophosphazene microscaffolds for the repair of infectious calvarial defect.

机构信息

State Key Laboratory of Organic-Inorganic Composites, Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing, China.

Department of Endodontics, School and Hospital of Stomatology, Tianjin Medical University, Tianjin, China.

出版信息

J Biomed Mater Res A. 2021 Dec;109(12):2580-2596. doi: 10.1002/jbm.a.37252. Epub 2021 Jun 26.

Abstract

Many osteoconductive and osteoinductive scaffolds have been developed for promoting bone regeneration; however, failures would occur in osteogenesis when the defect area is significantly infected while the biomaterials have no antibacterial performances. Herein, a kind of multipurpose PATGP@PDA + Ag microspheres was prepared via emulsion method by using a conductive aniline tetramer (AT) substituted polyphosphazene (PATGP), followed by polydopamine (PDA) modification and silver nanoparticles (AgNPs) loading. The PATGP@PDA + Ag microspheres demonstrated a strong antibacterial activity against Staphylococcus aureus both in vitro and in vivo, while showing no cytotoxicity at an optimized AgNPs loading amount. Due to the electron-donor structure of the AT moieties, the PATGP@PDA + Ag microspheres displayed antioxidant capacities to scavenge reactive oxygen species (ROS). Due to their phosphorus-rich feature, the PATGP@PDA + Ag microspheres favored the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). As controls, nonconductive microspheres (PAGP@PDA, PAGP@PDA + Ag) were prepared similarly by using poly[(ethylalanine)(ethylglycyl)]phosphazene (PAGP). By co-implanting these microspheres with S. aureus into rat calvarial defects, among them, it was determined that the PATGP@PDA + Ag microspheres achieved the most abundant neo-bone formation, benefiting from their antibacterial, antioxidant and osteogenic activities. These results revealed that AgNPs loaded scaffolds made of conductive polyphosphazenes were promising for the regeneration of infected bone defects.

摘要

已经开发出许多具有骨诱导和骨传导性能的支架来促进骨再生;然而,当缺损区域受到明显感染而生物材料没有抗菌性能时,成骨作用会失败。在此,通过乳液法制备了一种多功能 PATGP@PDA+Ag 微球,该方法使用导电苯胺四聚体(AT)取代的聚膦腈(PATGP),然后进行聚多巴胺(PDA)修饰和载银纳米颗粒(AgNPs)。PATGP@PDA+Ag 微球在体外和体内均表现出对金黄色葡萄球菌的强烈抗菌活性,而在优化的 AgNPs 载量下没有细胞毒性。由于 AT 部分的供电子结构,PATGP@PDA+Ag 微球表现出清除活性氧(ROS)的抗氧化能力。由于其磷含量丰富,PATGP@PDA+Ag 微球有利于骨髓间充质干细胞(BMSCs)的成骨分化。作为对照,通过类似的方法使用聚[(丙氨酸乙酯)(甘氨酸乙酯)]膦腈(PAGP)制备了非导电微球(PAGP@PDA、PAGP@PDA+Ag)。通过将这些微球与金黄色葡萄球菌共同植入大鼠颅骨缺损中,确定 PATGP@PDA+Ag 微球实现了最丰富的新骨形成,这得益于其抗菌、抗氧化和成骨活性。这些结果表明,负载 AgNPs 的导电聚膦腈支架有望用于感染性骨缺损的再生。

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